Cancer Chemopreventive Potential and Chemical Profiling of Euphorbia abyssinica Endowed with Docking Studies

[Image: see text] Chemical profiling of both fruit and aerial part extracts of Euphorbia abyssinica via ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) showed them to be a rich source of diverse compounds. A total of 39 compounds in both extracts including flavonoids and phenolic compounds were identified as predominant metabolites. The antioxidant activity of both extracts was evaluated using three different in vitro assays (DPPH, ABTS, and FRAP assays). The E. abyssinica fruit extract demonstrated more potent activity compared to the aerial part extract (IC(50) of 85.1 ± 1.07 and 562.3 ± 1.01 μg/mL, respectively) in the DPPH assay. Furthermore, using ABTS and FRAP assays, the antioxidant capacities of the fruit extract were 1063.03 ± 37.8 and 1476.5 ± 95.6, respectively, calculated as μM Trolox equivalent/mg extract. One of the existing markers for cancer chemoprevention is the induction of phase II detoxifying enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), which plays a vital role in cytoprotection against oxidative damage. The extracts were assessed to test their chemopreventive potential via NQO1 enzyme induction. The methanolic extract of fruits demonstrated a concentration-dependent increase in the cancer chemopreventive marker enzyme NQO1 at the protein expression level in a murine hepatoma cell line (Hepa1c1c7). The interaction with Kelch-like ECH-associated protein 1 (KEAP1) is an essential transcription factor that controls the expression of the NQO1 enzyme. The demonstrated induction of NQO1 by the fruit extract is consistent with a molecular docking study of the effect of dereplicated compounds on the KEAP1 target. Among the dereplicated compounds, hesperidin, naringin, and rutin have been established as promising inducer compounds for the chemopreventive marker NQO1. Our results highlight the E. abyssinica fruit extract as a future chemopreventive lead.